LOCAL ANAESTHETICS

Pharmacology
Local anaesthetics
Anaesthesia- complete or partial absence
of sensation to stimuli (e.g. cold, heat).

Since most surgical procedures require

cutting or painful manipulation, the
practitioner has to inject a local
anaesthetic to control pain and make the
procedure more comfortable.
Local anaesthetics
An ideal anaesthetic should have the following
characteristics:
a) Be able to induce anaesthesia smoothly and
rapidly and permit quick recovery as soon as
administration is stopped.
b) Produce a suitable state of analgesia and muscle
relaxation while remaining metabolically inert
and being rapidly eliminated.
c) Possess a wide safety margin and be free of
adverse effects.
 Local anaesthetics reversibly block the initiation and
propagation of action potentials or impulse conduction along
nerve axons and other excitable membranes that utilize
sodium channels as the primary means of action potential
generation, thus blocking pain sensations.
Local anaesthetics

 MOA- → prevents initiation and propagation of

action potentials → sodium channels blocked
(inactive) → via plugging of transmembrane pore.
This increases the threshold of excitation.

The rate, duration and extent of activity depends

on the type, caliber and site of nerve fibre, as
well as its degree of myelination and state of
activity.
Local anaesthetics
The effect of these drugs is more marked in
rapid firing axons than in resting fibres.

The smaller and more lipophilic the drug

molecule, the faster the rate of interaction with
the sodium channel receptor molecules.

The end result is motor paralysis.

Local anaesthetics
Administered as an injection into the area
of the nerve fibre to be blocked, or it can
be applied topically.

When injected, absorption and

distribution are not as important????
Local anaesthetics
Topical application of anaesthetics, however,
requires drug diffusion for both onset and offset
of the anaesthetic effect.

Effectsof local anaesthetics in the CNS, at low

doses →
sleepiness,
light headedness,
visual and auditory disturbances,
restlessness.
Local anaesthetics
At higher concentrations muscular
twitching may occur →convulsions
which can lead to CNS depression and
death.

Most serious toxic reactions are due to

convulsions from excessive blood
levels.
Local anaesthetics
Administration of larger doses requires
premedication with a benzodiazepine.

Mechanical ventilation may also be

required,
Local anaesthetics
2 classes of local anaesthetics:
◦ Amides: organic compounds that come from ammonia e.g.
lignocaine (Xylocaine®), bupivacaine (Marcaine®) &
mepivacaine.
◦ Esters: compounds formed from alcohols and acids by the
removal of water e.g. cocaine, procaine & propoxycaine.

 Esters are rapidly hydrolyzed by plasma cholinesterase, and

they are widely distributed because they are lipophilic.

 They are also converted in the liver by cholinesterases to more

water soluble metabolites, which are then excreted in urine.
Local anaesthetics
Amides are metabolized by liver
microsomal enzymes with variable, small
amounts excreted unchanged in the urine.

Conditions that reduce hepatic blood flow

will decrease hepatic removal of local
anaesthetics.
Local anaesthetics
The 2 most commonly used local anaesthetics
(amides) today are lignocaine hydrochloride and
bupivacaine.

Ester group is associated with a higher incidence

of allergic reactions band dependence than the
amide group, hence the amide group is preferred
to the esters for local use.
Local anaesthetics

o Choice of agent is based on the duration of

action required.

Vasoconstrictors like epinephrine can be

added?????

Onset of action can be accelerated by using

solutions saturated with carbon dioxide
Local anaesthetics
Local anaesthetics should be avoided in infected
or inflamed tissue.

Special care should also be taken in patients

with cardiac disorders especially when
vasoconstrictors are being used.
TOXICITY
CNS effects-
 Euphoria
 Sleepiness, light-headedness
 Visual and auditory disturbances
 Neurotoxicity
CVS effects-
 Depress normal pacemaker activity, excitability and
conduction.
 Decrease cardiac contractility and cause arteriolar
dilation (except cocaine).
 Local anaesthetics
 Lignocaine (lidocaine): most widely used local anaesthetic for IV regional
anaesthesia, nerve block and epidural anaesthesia and for topical anaesthesia.

 Adverse effects: usually dose-related, often resulting from inadvertent

intravascular administration.

− CNS side effects include: dizziness, light headedness, restlessness,

agitation and euphoria.

− With increasing toxicity there may be drowsiness, respiratory depression

and convulsions.

− Other effects include bradycardia, hypotension, cardiac arrhythmias,

occasionally nausea, vomiting and transient tinnitus.
 Local anaesthetics
Adult dose: individualized and adjusted according to
patient response and site of administration.

Generally a total dose of 3 mg/kg should not be

exceeded and if its combined with adrenaline, the
maximum dose is 6.5 mg/kg (not more than 500 mg).

Paediatric dose: maximum dose is 3 mg/kg with a

vasoconstrictor.
Bupivacaine
Long acting anaesthetic-useful during long
labour where the interval between doses is 2-3
hours.

Indications- epidural anaesthesia, epidural

analgesia.

A/E- dose related: dizziness, light-headedness,

agitation, depression, convulsions, euphoria.
THE END…